The overall objectives of this program/project are two-fold. The first is to develop methods of making human sequence variable antibody domains with combining specificity and affinity which are useful for human diagnosis and therapy. The second objective is to produce protein molecules which have defined amino acid alterations with the combining site so that methods of predicting the three dimensional conformation of a small portion of this protein can be tested, modified and improved. Chemical synthesis of the DNA to code for complementarity determining regions of the light and heavy chain variable regions will be combined with framework DNAs by using overlapping nucleotide sequences with suitable restriction endonuclease sites to make complete VL and VH genes. The medical uses of the material thus obtained would be for 1) combining with and eliminating a drug after the desired treatment time in cancer chemotherapy, 2) eliminating any undesirable small molecules from the serum resulting from drug overdose, 3) localizing by means of radioiodine coupling any identified cancer antigen, and 4) possible elimination of various receptors leading to the immediate allergic response. The program/project involves the collaborative work of several investigators: 1) a eukaryotic cell biologist working on the production in vivo or in vitro of large quantities of secreting human myelomia cells, 2) a protein physical biochemist, 3) a prokaryotic molecular biologist working on DNA cloning, sequencing and restriction mapping, 4) a eukaryotic molecular biologist working on the extraction and copying of mRNAs from mammals, and 5) a structural molecular biologist working on the calculations of protein conformations.